This application addresses the National Heart, Lung, and Blood Institutes Clinical Trial Pilot Studies (R34). Background: The optimal amount of calories and protein a critically ill patient should receive to reduce morbidity and mortality is unclear and remains controversial. Review of current practice in ICU patients indicates the actual amounts of enteral energy and protein delivered by standard hospital nutrition protocols is well below what is prescribed. U.S. ICU's were the least successful worldwide in delivering prescribed calories and protein. Despite aggressive, repeated efforts with guidelines and quality improvement initiatives over past years the amount of calories delivered via the enteral route has not significantly improved. Thus, if we are to successfully improve provision of energy and protein to patients at-risk of death from insufficient caloric delivery, we will have to supply calories via the intravenous parenteral nutrition (PN) route. Various national guidelines make different recommendations on the role of PN in the ICU, international audits show considerable practice variations, and existing clinical trial data, albeit it weak and outdated, are split on the use of PN in the early phase of critical illness (with some showing a mortality benefit and some showing no mortality benefit or possible increased infection risk from PN). However, a large recent observational research shows the amount of energy and protein received during the early stages of ICU admission impacts patient mortality, independent of route of delivery. This data from an international multicenter observational study of 2772 ICU patients in 165 ICUs who were expected to require mechanical ventilation for > 72 h found a significant inverse linear relationship between the odds of mortalit and total daily calories received. The key finding is that increased amounts of calories significantly reduced mortality for the patients with a BMI<25 and a BMI>35 with no benefit of increased calorie intake for patients in the BMI 25-<35 group. Feeding an additional 1000 kcals almost halved the odds of 60-day mortality in patients with a BMI <25 or >35. Similar results were observed for feeding an additional 30 grams of protein per day. Thus, Our Hypothesis is increased calorie and protein delivery to underweight and overweight critically ill patients with ARF (Body Mass Index [BMI] <25 or >35) will result in improved 60 day survival compared to usual care Our Specific Aim is to conduct a multinational, multicenter double-blind randomized controlled trial of EN plus supplemental PN vs EN and a parenteral placebo solution (standard care) in lean and obese critically ill patients with acute respiratory failure (ARF). Such a trial powered to show differences in 60-day mortality would require approximately 2000 patients. However, as we are uncertain of the feasibility and safety of conducting such a large study, thus in this application we propose pilot study of 160 patients in 6 centers will be conducted initially The main aim of the pilot study is to confirm we can safely achieve a clinically significant difference in caloric intake between the two study groups, without any increased risk from the supplemental PN. Study Design: The pilot study is a 6-center, double-blinded, placebo-controlled, randomized trial. Patients will be randomized to either: EN plus placebo PN solution or EN plus PN. Study Population: 160 critically ill patients with ARF (defined as expected to require mechanical ventilation > 72 h) to be initiated on EN within 48 h of ICU admission who have a pre-illness BMI < 25 and >35. Study Intervention: Eligible patients will be randomized within 48 h of ICU admission. In both groups, EN will be initiated and progressed to target dose according to a standard feeding protocol with a standard 1.2 kcal/ml formula. The intervention group will receive additional protein/energy via PN. This parenteral solution contains 1.2 cal/ml, similar to the EN solution. A placebo solution containing 1/2 normal saline will be used to maintain blinding in the control group. The relative amount of PN and EN will be monitored and adjusted daily to ensure that the patient receives 100% of prescribed calories daily. The supplemental PN solution or placebo PN will continue for 7 days. At the end of this study period, the study intervention will be stopped and clinicians can prescribe nutrition (PN or EN) as clinically indicated in both groups. Outcomes: This proposed pilot study will measure all clinical outcomes (e.g. mortality). The primary aim of this pilot study is to achieve a 30% difference in caloric and protein delivery difference (600-100 kcal/d and 20-30 g protein/d) between the control and intervention groups. Study patients will also be followed prospectively while in the ICU, to document compliance with the study intervention, maintenance of blinding, and adverse events. This will enable us to assess the feasibility of conducting the larger, definitive trial. Te results of this full-scale definitive study will serve to answer fundamental questions with regards to impact of amount of energy and protein delivered to nutritionally at-risk ICU patients and will for the first time in many years inform current practice on the use PN in the ICU.